1. Field of the Invention
This invention relates to novel amino-alcohol derivatives and more particularly to amino-alcohol derivatives of the formula (I), ##STR2## where R.sub.1 is a straight or branched alkyl group having 3 to 8 carbon atoms, R.sub.2 and R.sub.3 are each a lower alkyl group, or R.sub.2 and R.sub.3 form a 5- to 7-membered ring together with the adjacent nitrogen atom which may have an oxygen atom attached thereto, R.sub.4 is a hydrogen atom or a lower alkyl group, R.sub.5 is a hydrogen atom or a lower alkyl group, X is a hydrogen or halogen atom or a lower alkyl or lower alkoxy group, and n is an integer of 2 or 3, or acid addition salts thereof. The invention further relates to processes for preparing these compounds.
2. Description of the Prior Art
As has been strongly suggested in the art, glutamic acid acts as an excitatory neurotransmitter at the central nervous systems of higher animals and at the neuromuscular junctions of lower animals ["Glutamate as a Neurotransmitter" edited by G. D. Chiara & G. L. Gessa: Raven Press, New York, 1981 and H. M. Gerschenfeld: Physiol. Rev., 53, 1-119 (1973)]. It has also been reported that dystropy, rigidity, tremors, convulsions and the like are induced by the administration of kainic acid, domoic acid, quisqualic acid, ibotenic acid or the like, which acids are extremely strong agonists for glutamic acid in higher animals [Oleny et al.: Brain Res., 77, 507-512 (1974)].
It is known that as aging proceeds, the central and peripheral nervous systems would undergo hypoergia to develop Parkinson's disease, motoneuron disorders, dementia, tremors, spinocerebellar degeneracy and the like. These diseases are considered to be attributable to off-balanced equilibration between excitatory nerves and inhibitory nerves (for example, the equilibration between glutamic acid and GABA) due to loss of neurons at certain specific sites or overall hypoergia of the nervous systems [Toshishige Hirai: Shinkei Shimpo, 17, 69 (1973)].
With the foregoing in view, medicines that can selectively block glutamic acid are useful for the therapy of neuropathy from which the senile would most often suffer and which would involve such complaints as vertigo, shoulder discomfort, convulsions, tremors and the like, all of them resulting from off-balanced nervous systems or hyperstenia in muscle discharge.
Glutamic acid also acts as an excitatory neurotransmitter for neuromuscular junctions of insects. Chemicals capable of blocking glutamic acid are therefore suitable for agricultural use for their ability to reduce and weaken insects' activities [Morifusa Eto: Kagaku to Seibutsu, 21, 725 (1983)].
It has now been found that amino-alcohol derivatives of the formula (I) above have excellent blocking effects against glutamic acid as well as neuraxial muscle relaxing effects, i.e. rigidity reducing and releasing effects on anemic decerebrate rigidity samples.
This result suggests that the inventive compounds are useful for the therapy of a complaint which would have spastic paralysis and rigidity and these compounds are expected to suppress or release dyskinasis, athetosis, myoclonus, tic, tremors, dystonia and ballismus of neuropathy.
Some compounds are known which are structurally similar to the compounds contemplated by the present invention. Such known compounds are 2-(2-dimethylaminoethylamino)-1-phenylpropan-1-ol [Sv. Zikolova and L. Zhelyazkov: Tr. Nauchno-Izsled. Inst. Farm., 3, 14-19 (1961) (CA, 61, 9485b)], 1-phenyl-2-(2-piperidinoethylamino)propan-1-ol and 1-phenyl-2-(2-pyrrolidinoethylamino)propan-1-ol [ibid., L. Zhelyazkov, A. Georgiev, Sv. Zikolova, P. Manolov, L Daleva and M. Kazandzhiev: Tr. Nauchnoizsled. Khim.-Farm. Inst., 1972, 7, 33-53 (CA, 79, 27099g) and L. Daleva, P. Manolov: Tr. Nauchnoizsled. Khim.-Farm. Inst., 1972, 7, 229-240 (CA, 79, 27213g)]and 2-(2-morpholinoethyl- amino)-1-phenylpropan-1-ol [Sv. Zikolova and L. Zhelyazkov: Farmatsiya, 14, (5), 16-21 (1964) (CA, 62, 13135g)]. These prior art publications however are silent as to whether the known compounds would have blocking effects against glutamic acid. Experiments conducted by the present inventors show that those compounds are only marginal in their glutamic acid blocking effects and in their rigidity reducing and releasing effects as compared with the compounds of the invention.